
from rdkit import Chem
from rdkit.Chem import AllChem
from rdkit import RDConfig
from rdkit.Chem.Draw import IPythonConsole 
from rdkit.Chem import Draw
import numpy as np
from IPython.display import display,Image
import rdkit.Chem.Lipinski as Lipinksy
import pubchempy as pcp


ibu=Chem.MolFromSmiles('CC(C)CC1=CC=C(C=C1)C(C)C(=O)O')
AllChem.Compute2DCoords(ibu)
display(ibu)


compounds = []
per_page = 1000
for smiles in ["N=[N+]=[N-]", "N=N=N", "NN#N"]:
    for i in range(2):
        try:
            a = pcp.get_properties(properties = "CanonicalSMILES", 
                                   identifier = smiles, namespace="smiles", 
                                   searchtype = "substructure", 
                                   RingsNotEmbedded = True, 
                                   listkey_count = per_page, 
                                   listkey_start = i*per_page)
        except:
            None
        print ("Retrieved page {} of {} search".format(i+1, smiles))
        compounds.extend(a)

Retrieved page 1 of N=[N+]=[N-] search
Retrieved page 2 of N=[N+]=[N-] search
Retrieved page 1 of N=N=N search
Retrieved page 2 of N=N=N search
Retrieved page 1 of NN#N search
Retrieved page 2 of NN#N search


smiles_list = [k['CanonicalSMILES'] for k in compounds]#создадим список из SMILES


template = 'N1N=NC(=C1)C(C)(C(=O)O)C1=CC=C(C=C1)CC(C)C'
template_mol = Chem.MolFromSmiles('N1N=NC(=C1)C(C)(C(=O)O)C1=CC=C(C=C1)CC(C)C')
AllChem.Compute2DCoords(template_mol)
display(template_mol)


new_smiles = []

for smi in smiles_list:
    for a in ["N=[N+]=[N-]", "N=N=N", "NN#N"]:
        if a in smi:
            newsmi = smi.replace(a, template)
            new_smiles.append(newsmi)


def is_lipinsky(smiles, parameters=(5, 10, 500, 5)):
    return all(i < j for i, j in zip([Lipinksy.NumHDonors(smiles),
                Lipinksy.NumHAcceptors(smiles),
                Lipinksy.rdMolDescriptors.CalcExactMolWt(smiles),
                Lipinksy.rdMolDescriptors.CalcCrippenDescriptors(smiles)[0]], parameters))
is_lipinsky(ibu)

True


#проверим на отобранных молекулах правило Липински
lep_mol = []

for smi in new_smiles:
    try:
        newmol=Chem.MolFromSmiles(smi)
        if is_lipinsky(newmol) == True:
            lep_mol.append(newmol)
    except:
        pass

RDKit ERROR: [20:42:35] Explicit valence for atom # 8 Cl, 3, is greater than permitted
RDKit ERROR: [20:42:38] Explicit valence for atom # 8 Cl, 3, is greater than permitted


print("Молекул, удовлетворяющих правилу Липински, {} шт. из {} найденных по шаблону.".format(len(lep_mol),len(new_smiles)))

Молекул, удовлетворяющих правилу Липински, 446 шт. из 4001 найденных по шаблону.


from IPython.display import SVG

for mol in good_mol:
    AllChem.Compute2DCoords(mol)
display(Draw.MolsToGridImage(good_mol[:64],useSVG=True, molsPerRow=3, subImgSize=(200, 200)))

/mnt/scratch/mm-course/miniconda3/envs/molsim/lib/python3.6/site-packages/rdkit/Chem/Draw/IPythonConsole.py:188: UserWarning: Truncating the list of molecules to be displayed to 50. Change the maxMols value to display more.
  % (maxMols))


from rdkit.Chem.Draw import SimilarityMaps
fp = SimilarityMaps.GetMorganFingerprint(lep_mol[5], fpType='bv')
fig, maxweight = SimilarityMaps.GetSimilarityMapForFingerprint(ibu, lep_mol[5], SimilarityMaps.GetMorganFingerprint)


conda install -c omnia nglview

Collecting package metadata (current_repodata.json): done
Solving environment: done


==> WARNING: A newer version of conda exists. <==
  current version: 4.8.2
  latest version: 4.10.1

Please update conda by running

    $ conda update -n base -c defaults conda


## Package Plan ##

  environment location: /mnt/scratch/mm-course/miniconda3/envs/molsim

  added / updated specs:
    - nglview


The following packages will be downloaded:

    package                    |            build
    ---------------------------|-----------------
    ca-certificates-2021.4.13  |       h06a4308_1         114 KB
    nglview-0.6.2.3            |           py36_0         5.2 MB  omnia
    openssl-1.1.1k             |       h27cfd23_0         2.5 MB
    ------------------------------------------------------------
                                           Total:         7.8 MB

The following packages will be UPDATED:

  ca-certificates    conda-forge::ca-certificates-2020.12.~ --> pkgs/main::ca-certificates-2021.4.13-h06a4308_1
  openssl                                 1.1.1j-h27cfd23_0 --> 1.1.1k-h27cfd23_0

The following packages will be SUPERSEDED by a higher-priority channel:

  nglview            conda-forge/noarch::nglview-2.7.7-pyh~ --> omnia/linux-64::nglview-0.6.2.3-py36_0


Downloading and Extracting Packages
ca-certificates-2021 | 114 KB    | ##################################### | 100% 
nglview-0.6.2.3      | 5.2 MB    | ##################################### | 100% 
openssl-1.1.1k       | 2.5 MB    | ##################################### | 100% 
Preparing transaction: done
Verifying transaction: failed

EnvironmentNotWritableError: The current user does not have write permissions to the target environment.
  environment location: /mnt/scratch/mm-course/miniconda3/envs/molsim
  uid: 10517
  gid: 1018


Note: you may need to restart the kernel to use updated packages.


import nglview as nv


m3d=Chem.AddHs(lep_mol[5])
Chem.AllChem.EmbedMolecule(m3d)
AllChem.MMFFOptimizeMolecule(m3d,maxIters=500,nonBondedThresh=200 )
m3d


nv.show_rdkit(m3d)